There are several drugs for human immunodeficiency virus (HIV) at present and some of these target nucleosides called nucleoside analogues. There are also those medications which target the reverse transcripase enzyme of the virus, also known as the non-nucleoside reverse-transcriptase inhibitors (Neal 2005). Nucleoside analogues compete with naturally occurring nucleosides in the cell which aids in the coding of the viral RNA into full strand DNA. The nucleoside analogues terminate the chains in the formation of DNA by incorporating dideoxynucleotide, thus stopping the process of forming DNA. And with this, the viral strands are not prevented from replicating. An example of a reverse transcriptase inhibitor is the drug Zidovudine (Lipsky 1996).
Chemical structure of the anti-viral drug Zidovudine
The non-nucleoside reverse transcriptase inhibitors on the other hand prevent the replication of viral DNA by targeting reverse transcriptase enzymes which are necessary in the synthesis of DNA (Rang et al 2003). By reversing the function of reverse transcriptase enzymes, the virus is unable to replicate.
HIV Proteases and Aprenavir
HIV proteases are protein structures that play a role in the cataylsis of HIV’s peptide bonds. This is necessary for the virus’ life cycle. With the protease being able to synthesize polyproteins to produce mature protein components, the HIV will then become infectious (Lipsky 1996).
The protein structures of HIV proteases are of a retroviral aspartyl protease type. The HIV protease acts by cleaving the peptide bond between an aromatic amino acid and proline. Throughout the process, mature protein products are released which are crucial for viral replication (Brick and Wong 2002). According to Lipsky (1996), if the proteins weren’t cleaved, then HIV won’t be in an infectious state.
In connection to HIV proteases, an HIV protease inhibitor drug called Aprenavir was developed by Glaxo. The design of this drug is based on computer assisted drug design technology combined with crystallography. In several clinical trials with patients, it has been noted to have good potency. Also noted further is its characteristic of being synergistic with the activities of other antiviral drugs such as Zidovudine and Saquinavir . The general principles behind its design was that the drug shared common features with other protease inhibitors like Squinavir. Aprenavir though differing in its functional groups on both ends of its structure and also having few chiral centers, this drug is easier to synthesize and has greater water solubility (Tomasselli and Heinrikson 1999).
Antiretroviral drugs in HIV are still a focus of study at present. With the global pandemic that's going on caused by the novel coronavirus covid-19, several scientists are exploring the actions of several anti-viral drugs which includes HIV medications in hopes of finding possible biochemical targets that may interfere with the viral replication of covid-19 in ACE-2 expressed human cells.
References:
Braunwald, E., Fauci, A., Kasper, D., Hauser, S., Longo, D. And Jameson, J.L. (2001). Harrison’s Principles of Internal Medicine. 15th Edition. New York. McGraw-Hill. pp.225-226
Brick, A. and Wong, C. (2002). HIV-1 Protease: Mechanism and Drug Discovery. (online) Available at: http://iverson.cm.utexas.edu/courses/310N/ROTDSp06/HIVMechanismDrugDesign.pdf (Accessed: May 28, 2015)
Ford, C. (2001). First of a Kind. (online). Available at: https://learn2.open.ac.uk/pluginfile.php/1382158/mod_resource/content/2/Ford_2001.pdf (Accessed: June 10, 2015)
Lipsky, J. (1996). Antiretroviral drugs for AIDS. Lancet, 348:800-03. (online) Available at: https://learn2.open.ac.uk/pluginfile.php/1382162/mod_resource/content/2/Lipsky_1996.pdf (Accessed: June 9, 2015).
McMurry, M. (1998). Fundamentals of Organic Chemistry. 4th Edition. Singapore. Thomson Learning Asia Publishing Ltd.
Rang, H.P., Dale, M.M., Ritter, J.M., and Moore, P.K. (2003). Pharmacology. Fifth Edition. Philadelphia. Elsvier Science Limited.
Tomasselli, A. and Heinrikson, R. (1999). Targeting HIV-protease in AIDS therapy: a current clinical perspective. (online). Available at: https://learn2.open.ac.uk/pluginfile.php/1382165/mod_resource/content/1/Tomasselli.pdf (Accessed at: June 10, 2015).
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